RESUMEN
Autosomal dominant and recessive mutations in COL12A1 cause the Ehlers-Danlos/myopathy overlap syndrome. Here, we describe a boy with fetal hypokinesia, severe neonatal weakness, striking hyperlaxity, high arched palate, retrognathia, club feet, and pectus excavatum. His motor development was initially delayed but muscle strength improved with time while hyperlaxity remained very severe causing recurrent joint dislocations. Using trio exome sequencing and a copy number variation (CNV) analysis tool, we identified an in-frame de novo heterozygous deletion of the exons 45 to 54 in the COL12A1 gene. Collagen XII immunostaining on cultured skin fibroblasts demonstrated intracellular retention of collagen XII, supporting the pathogenicity of the deletion. The phenotype of our patient is slightly more severe than other cases with dominantly acting mutations, notably with the presence of fetal hypokinesia. This case highlights the importance of CNVs analysis in the COL12A1 gene in patients with a phenotype suggesting Ehlers-Danlos/myopathy overlap syndrome.
Asunto(s)
Síndrome de Ehlers-Danlos , Enfermedades Musculares , Colágeno Tipo XII/genética , Variaciones en el Número de Copia de ADN , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Exones , Humanos , Hipocinesia/genética , Masculino , Enfermedades Musculares/genética , MutaciónRESUMEN
Paediatric intracranial vascular malformations are rare and different from adult ones in vascular anatomy, pathophysiology, and symptoms. Their impact on the brain and their symptoms will differ in the antenatal period, in neonates, infants, and children. Clinical presentation includes seizures, focal neurological deficit, haemorrhage, congestive heart failure, hydrovenous disorder, and developmental delays. These malformations are thus associated with a poor prognosis if left untreated. Therefore, aggressive management is generally recommended and must be performed by a multidisciplinary team with extensive experience. Endovascular treatment is the first-choice treatment for most paediatric intracranial vascular malformations. Indication and timing for treatment should be decided on the basis of a careful assessment of neurological symptoms, growth and development, cardiac and other systemic manifestations, and imaging of the malformation and the brain tissue. WHAT THIS PAPER ADDS: Paediatric intracranial vascular malformations are rare, but their prognosis is poor if left untreated. Improved clinical, anatomical, and pathophysiological understanding of these complex lesions has improved prognosis.
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Malformaciones Vasculares del Sistema Nervioso Central/terapia , Venas Cerebrales/anomalías , Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Angiografía Cerebral , Venas Cerebrales/diagnóstico por imagen , Niño , HumanosRESUMEN
Introduction: We describe the first case of acute flaccid myelitis (AFM) related to enterovirus D68 (EV-D68) infection in Belgium. The clinical and radiological presentation of AFM associated with EV-D68 although well described currently remains a challenging diagnosis. Through this interesting clinical case, we aimed to review the differential diagnosis of acute flaccid palsy in a child and discuss the specific point of interest related to AFM. Case Presentation: We present the case of a 4-year-old girl with a torticollis associated with an acute palsy of the right upper limb. The magnetic resonance imaging revealed an increased T2 signal intensity of the entire central gray matter of the cervical cord with involvement of the posterior brainstem. A polymerase chain reaction (PCR) conducted on a nasopharyngeal swab was found positive for EV-D68. The definition of AFM proposed by the Center for Disease Control and Prevention (CDC) is an acute-onset flaccid weakness of one or more limbs in the absence of a clear alternative diagnosis and the radiological evidence of gray matter involvement on an MRI picture, and our case fits these two criteria. A prompt and detailed workup is required to distinguish this emergent disease from other forms of acute flaccid palsy. The functional prognosis of AFM is poor, and there are no evidence-based treatment guidelines so far. Conclusion: AFM is an emerging pathology that requires the attention of pediatricians to quickly rule out differential diagnoses and adequately manage the patient. Further research is needed to optimize treatments, improve outcomes, and provide scientifically based guidelines.
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BACKGROUND AND PURPOSE: The contribution of MR imaging to identify hypoxic-ischemic injuries has been studied mostly in neonates or adults. The purpose of this study was to describe the MR imaging findings of toddlers and older children with hypoxic coma and to analyze the prognostic value of an MR imaging scoring system. METHODS: The conditions of 40 children with hypoxic coma (age range, 6 weeks to 18 years) were clinically graded according to the pediatric risk of mortality score, and MR imaging studies were performed. Sixty-four MR imaging studies were distributed in five categories according to their timing relative to the hypoxic event: days 1 through 3, 4-7, 8-15, 16-50, and after day 50. These were evaluated retrospectively by using an eight-point scoring system based on two lesion categories assessing watershed areas and basal ganglia involvement, including signal intensity and morphologic features with respect to maturation-related norms. Two age groups (< or =1 year and >1 year) were considered. The surviving children were grouped according to neurologic outcome. RESULTS: The occurrence of watershed areas or basal ganglia involvement was not significantly different in association with age. Sixteen children died. Twelve children had moderate to severe sequelae resulting from neurodevelopmental disabilities, and 12 had good neurologic outcomes. There was no correlation between pediatric risk of mortality score and neurologic evolution. There was a strong correlation between first MR imaging score (P <.001) and neurologic outcome. The sensitivity of the first MR imaging score was high (96%), even when obtained during the first 3 days, with a specificity of 50% and a positive predictive value of 82%. Six patients with definite abnormal MR imaging findings experienced good neurologic outcomes. CONCLUSION: The MR imaging scoring system proposed in this study can be used to establish an early prognosis in a significant proportion of children with hypoxic coma. It is helpful, even during the first 3 days after the event. However, some patients with definite abnormal MR imaging findings may experience good neurologic evolution.
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Encéfalo/patología , Coma/patología , Hipoxia Encefálica/patología , Imagen por Resonancia Magnética , Adolescente , Ganglios Basales/patología , Niño , Desarrollo Infantil , Preescolar , Coma/etiología , Coma/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Hipoxia Encefálica/complicaciones , Hipoxia Encefálica/mortalidad , Lactante , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
In spastic diplegia impaired postural control jeopardizes the organization of whole-body movements. We studied segmental motor patterns involved in standing up from a supine position in ten children with spastic diplegia associated with periventricular leukomalacia and 14 unimpaired children using a visual analysis scale previously devised for developmental research. This approach examines specific movement patterns in upper limbs, axis and lower limbs. We found that children with spastic diplegia use movement patterns described in normal children but with markedly reduced intra- and interindividual variability. One previously undescribed stereotyped lower limb pattern was observed in four patients. This approach can systematically characterize the limited repertoire of movement in patients with spastic diplegia and therefore contribute to a better understanding of motor control.
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Parálisis Cerebral/fisiopatología , Leucomalacia Periventricular/complicaciones , Movimiento , Postura , Fenómenos Biomecánicos , Parálisis Cerebral/etiología , Niño , Preescolar , Femenino , Humanos , Recién Nacido , Leucomalacia Periventricular/fisiopatología , Masculino , Destreza MotoraRESUMEN
Isolated status epilepticus or severe hypoglycemia rarely causes irreversible focal neurologic deficits in children. We describe three children who presented with status epilepticus and prolonged hypoglycemia resulting in hemiplegia due to unilateral hemispheric damage. The non-vascular cortical topography of the lesions is consistent with selective neuronal necrosis, confirmed by histopathology in one patient. This suggests increased neuronal vulnerability to necrosis secondary to energy failure resulting from combination of hypoglycemia and status epilepticus.
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Corteza Cerebral/patología , Hipoglucemia/complicaciones , Estado Epiléptico/complicaciones , Estado Epiléptico/patología , Daño Encefálico Crónico/complicaciones , Daño Encefálico Crónico/diagnóstico , Niño , Preescolar , Enfermedad Crónica , Femenino , Hemiplejía/etiología , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , NecrosisRESUMEN
Visual symptomatology in childhood often presents diagnostic difficulties. Recurrent paroxysmal visual complaints, although typically associated with migraine, may also signal other disorders. We describe a 9-year-old partially sighted male with paroxysmal zoopsias resulting from Charles Bonnet syndrome. This condition is characterized by paroxysmal visual hallucinations occurring in patients with chronic visual impairment, akin to the phantom-limb phenomenon. This pediatric case is the fourth report of this condition. We have reviewed the other cases.
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Ceguera/complicaciones , Alucinaciones/etiología , Oftalmoplejía/complicaciones , Trastornos de la Percepción/etiología , Percepción Visual/fisiología , Atrofia , Corteza Cerebral/patología , Niño , Humanos , Imagen por Resonancia Magnética , Masculino , SíndromeRESUMEN
Although subacute ascending paralysis without sensory involvement is typically evocative of Guillain-Barré syndrome, it can alternatively be due to infection or inflammation of the spinal cord. We describe a 16-month-old female who presented with ascending flaccid paresis after an upper respiratory tract infection. She then developed signs of upper motor neuron involvement of the lower limbs associated with upper motor neuron involvement of the upper limbs. Motor nerve conduction and electromyographic studies of upper limbs demonstrated anterior horn cell involvement. Neuroimaging was consistent with cervical myelitis, and cerebrospinal fluid polymerase chain reaction was positive for herpesvirus-1. Although association with the primary infection of the respiratory tract may be fortuitous, possible neurotropic or hematogenous spread of herpesvirus-1 to the cervical spinal cord cannot be excluded. She then developed signs of upper motor neuron involvement of the lower limbs associatred with lower motor neuron involvement of the upper limbs [corrected].
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Vértebras Cervicales/patología , Vértebras Cervicales/virología , Herpes Simple/patología , Herpesvirus Humano 1 , Mielitis/patología , Mielitis/virología , Femenino , Herpes Simple/virología , Humanos , LactanteRESUMEN
Cerebellar mutism (anarthria) is a well-described complication of posterior fossa tumor resection. It is accompanied by a characteristic behavior including irritability and autistic features. This syndrome is typically reversible within days to months. Underlying pathophysiology is unknown. We describe two children who presented with a similar clinical finding after nonsurgical cerebellar involvement, hemolytic-uremic syndrome in one and cerebellitis in the other. Postmortem pathologic findings in the first patient indicated cerebellar ischemic necrosis. Single-photon emission computed tomography in the second patient revealed diffuse cerebellar hypoperfusion with no supratentorial abnormalities, refuting a phenomenon of diaschisis between cerebellar and frontal connections. These findings confirm that this clinical syndrome may occur in a nonsurgical, nontraumatic context. They are consistent with recent integrative hypotheses explaining cerebellar anarthria.
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Enfermedades Cerebelosas/patología , Cerebelo/patología , Mutismo/patología , Enfermedades Cerebelosas/etiología , Preescolar , Encefalitis/complicaciones , Femenino , Síndrome Hemolítico-Urémico/complicaciones , Humanos , Imagen por Resonancia Magnética , Mutismo/etiologíaRESUMEN
Assessment of prognosis of children in hypoxic coma is difficult. The value of clinical evaluation is often limited. The usefulness of electrophysiologic tests has been documented mostly in adults and neonates and in cases of traumatic coma. We reviewed retrospectively 39 consecutive children with nontraumatic hypoxic coma to assess the prognostic value of EEG, visual, and auditory evoked potentials. Correlation between electrophysiology and neurologic outcome after mean follow-up period of 30 months was significant (r(s) = 0.6, P < 0.001). In contrast there was no correlation between Pediatric Risk of Mortality score (PRISM) and outcome (r(s) = -0.42, P = 0.8). Combining magnetic resonance imaging with electrophysiology further enhanced their prognostic value (r(s) = 0.69, P < 0.001). Neuroimaging was highly sensitive but less specific, and electrophysiologic tests were highly specific but less sensitive. We conclude that early electrophysiology can contribute to predicting outcome in pediatric hypoxic coma.
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Coma/diagnóstico , Hipoxia Encefálica/diagnóstico , Adolescente , Niño , Preescolar , Coma/fisiopatología , Electroencefalografía/métodos , Electrofisiología , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Visuales/fisiología , Femenino , Humanos , Hipoxia Encefálica/fisiopatología , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
OBJECTIVE: We investigated a large consanguineous Moroccan family with progressive myoclonic epilepsy (PME) consistent with autosomal recessive inheritance, to describe the phenotype and identify the causal gene. METHODS: We recorded the clinical course of the disease and the response to drug therapy, whereas carefully excluding known causes of progressive myoclonic epilepsy. We then linked the disease by homozygosity mapping using microsatellite markers and single nucleotide polymorphism microarrays (11K GeneChip), and studied candidate genes in the critical linkage region. RESULTS: Epilepsy started between 16 and 24 months of age after normal initial development. Seizures were multifocal myoclonus aggravated by movements, and generalized tonic-clonic seizures were experienced by two patients. Electroencephalogram showed slow dysrhythmia, multifocal and occasionally generalized epileptiform discharges, and photosensitivity. Brain magnetic resonance images were normal. All patients were demented. Two had refractory epilepsy and a severe course. Seizures were controlled in the third patient, whose disease course was less severe. Linkage analyses identified a new locus on 7q11.2, with a maximum multipoint logarithm of odds of 4.0 at D7S663. In the critical linkage region, we found a C to T mutation in exon 2 of the potassium channel tetramerization domain containing 7 gene (KCTD7). The mutation affected a highly conserved segment of the predicted protein, changing an arginine codon into a stop codon (R99X). INTERPRETATION: Neurodegeneration in progressive myoclonic epilepsy presented by our patients paralleled the refractoriness of epilepsy. The disease was transmitted as an autosomal recessive trait linked to a novel locus at 7q11.2, where we identified a mutation in KCTD7.